DNA insertion elements represent an important pathway for the reassortment of genetic information and the evolution of chromosome primary structure in bacteria. We propose that similar elements in mammalian cells may be involved in the formation of chromosome abnormalities in cancer cells. Transposable elements carrying antibiotic resistance genes (transposons) represent a particular class of DNA insertion elements. Ease of detection and selection for drug-resistance markers makes them especially good experimental material. It is known that transposons move from one genetic site to another by special mechanisms independent of general homologous recombination functions. They are also involved in other genetic events such as deletion fromation. All transposons so far examined have similar structural pattern: resistance genes bounded by repeated sequences. The structural and enzymatic details of the transposition mechanism remain to be eluciated. Moreover, the effect of agents which react with DNA (particularly carcinogens) on the transposition process is unknown. Thus, we propose to extend our previous work on several transposons to (1) develop an in vitro transposition assay, (2) examine the importance of terminal repeat structures for the transposition process, and (3) test whether carcinogens stimulate the trasnsposition process. Our methods include the isolation of circular DNA forms which may be intermediates in the transposition of Tn9 (chloramphenicol-resistance transposon), restriction enzyme deletion formation to determine the role of the terminal repeat IS1 sequences in Tn9, use of the high frequency transposition of Tn401 (carbenicillin-resistance transposon) in P. putida cells to develop an in vitro transposition assay, genetic and heteroduplex studies of Tn402 (trimethoprim-resistance transposon) to test the generality of the terminal repeat structure, and use of a lambda transposition assay to measure the effects of carcinogens on transposition frequencies.